Project Summary/Abstract Nonalcoholic fatty liver disease (NAFLD) affects one in three adults and one in five children in North America and is a growing public health issue in the United States and many parts of the world. NAFLD, and especially nonalcoholic steatohepatitis (NASH), may lead to cirrhosis requiring liver transplant, and liver cancer, as well as liver-, cardiovascular-, and cancer-related morbidity and mortality, resulting in increased health burdens and associated costs. The Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) has been sponsored by the National Institutes of Health (NIH) since 2002 and has provided important information regarding the natural history and treatment of NAFLD and NASH in adults and children, and has set the stage for translational research focused on the pathogenesis, diagnosis, treatment, and clinical management of these patients. This application is in response to the Limited Competition for the Continuation of the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Data Coordinating Center (DCC) (RFA-DK-18-506). Our aims for the continuation in response to the RFA are: 1) To complete the pediatric treatment trial initiated during the previous funding cycle; 2) To develop and conduct a new adult phase 2 treatment trial; 3) To coordinate the concepts, development, vetting, and selection by the Steering Committee and NIDDK of additional clinical trials in adults and children of novel therapeutic strategies; 4) To coordinate and facilitate synergistic partnerships between NASH CRN investigators and expert scientists to use biospecimens, histology, digital imaging, and clinical meta-data to derive novel non-invasive biomarkers and advance the understanding of genomic, proteomic, lipidomic, metabolomic, and microbiomic determinants of the pathogenesis and progression of NASH; 5) To coordinate the development of a natural history cohort study of NAFLD, including both hepatic and non-hepatic outcomes; 6) To coordinate and implement use of a centralized IRB (sIRB) to oversee all future NASH CRN studies. The Data Coordinating Center will provide the NASH CRN with leadership, expertise in biostatistical analysis, study design, data management, multicenter coordination, quality control methods, safety oversight, project support, communication, and organization, and is eager to continue its collaboration with the clinical centers, NIDDK program staff, and private sector partners to complete these important research objectives. The NASH CRN is poised to continue its major impact on the field and directly advance the mission of the National Institutes of Health to improve the health of the public.